Abstract

Objectives: Endovascular treatment of intracranial aneurysms using detachable coils is an established method by interventional radiologists. Next to prevention of subarachnoidal hemorrhage, prospective and retrospective studies have shown relief of symptoms caused by the mass effect of the aneurysm following this treatment.

Patients and methods: We present cases of endovascular treated intracranial aneurysms in patients developing focal neurological symptoms due to a local perianeurysmal inflammation. Furthermore, we review the literature to increase awareness of this complication, its pathophysiology and therapeutic options.

Results: Only rare cases of local perianeurysmal inflammation have been reported in literature. Clinical symptoms are heterogenous, up to focal seizures or symptoms of acute hydrozephalus. Pathophysiological, thrombembolism, local inflammatory and mass are possible aetiological factors. However, overall long-term prognosis is good.

Conclusion: Neurovascular compression syndrome after intracraniel aneurysm coiling is a rare and possibly delayed complication. With regard to various causes, diagnostic and therapeutic options should be considered.

Introduction

Endovascular treatment of aneurysms using detachable coils
has evolved as a preferred alternative to classical surgical clipping to
prevent rupture and subarachnoidal haemorrhage. For aneurysms
located within the vertebrobasilar circulation, in particular, this
treatment is first choice. Coil-induced closure of the aneurysm sac
finally may reduce the lesion’s mass effect on surrounding tissue with
a consequent reduction in neurological symptoms, if symptoms due
to mass effect occurred. Most reported complications of endovascular
coiling include coil displacement, aneurysm rupture or puncture,
artery dissection, and cerebral embolism. Only anecdotal information
exists on progression of aneurysm size, local inflammation, and abscess
formation after endovascular treatment. First, we present the case of
a 49-year-old woman in whom a complex set of complications arose
after aneurysm coiling and discuss current views on the subject and
possible therapeutic options for rare side effects. In a second case we
report about a 62-year-old man suffering from reduced consciousness,
hemiparesis and dysarthria about three weeks after successful coiling of
two intracranial aneurysms.

Patients and Methods

Case 1: A 49-year-old woman was admitted to the hospital for mild
right-sided hemiparesis due to an ischemic stroke in the subcortical white
matter of the left hemisphere, which was classified as a lacunar stroke. During a diagnostic workup an asymptomatic aneurysm of the basilar
artery was found (Figure 1). Diagnostic intra-arterial digital subtraction
angiography (DSA), performed before interventional treatment,
revealed that the aneurysm measured 9 × 6 mm and was accompanied
by a small daughter aneurysm. Coils were placed in successful in both
aneurysms. At the end of the procedure, a small coil loop could be seen
to protrude from the larger compartment overlapping the small side
aneurysm (Figure 1). Eight hours after the intervention the patient
developed bilateral mydriasis, which was followed by a progressive loss
of consciousness. Emergency cerebral CT scanning with CTA ruled
out the presence of aneurysm bleeding or ruptures but showed partial
obliteration of the P1 section of both posterior cerebral arteries (PCAs).
IV treatment with the gpIIb/IIIa inhibitor (tirofiban) was introduced.
Immediate DSA confirmed the findings of the CTA with intraluminal
sparing of contrast media, which were suggestive of fresh thrombotic
material in both PCAs (Figure 2). After local thrombolytic treatment
with 4 mg rtPA, the patient recovered well. MRI revealed multiple
small ischemic lesions with haemorrhagic transformation within
the cerebellum and PCA territories; however, the patient showed no
neurological deficits and was discharged from the hospital 5 days later.
The patient was sent home on a regimen of acetylsalicylic acid (100 mg/
day) and low-molecular-weight heparin (certoparin) for thrombosis prophylaxis. One week later the patient presented at the emergency
room with progressive headaches and undulating double vision as well as right-sided mydriasis (Figure 3). A complete workup showed only
a mildly elevated red blood cell count in CSF obtained from lumbar
puncture and no sign of a disturbance in the blood-brain barrier. MRI
revealed mesencephalic oedema on FLAIR sequence without changes
on DWI or ADC (Figure 4). Over the course of the next week, the
patient’s double vision worsened due to left-beating nystagmus (Figure
3). Despite escalated anti-inflammatory and anti-oedematous therapy
consisting of steroids and glycerol, follow-up MRI showed progressive
mesencephalic oedema and, finally, evidence of ischemic stroke (Figure
4). The patient’s symptoms gradually stabilized. She was transferred
to a neurological rehabilitation centre with persistent double vision
and was given antithrombotic therapy consisting of clopidogrel and
certoparin. At the 3-month follow-up examination, the woman’s
oculomotor palsy was no longer detectable, but her intermittent double
vision while looking to the left still persisted (Figures 3C and D). MRIs
indicated a small post-ischaemic mesencephalic defect with no further
evidence of oedema.

Figure 1: First case: 49-year-old woman after lacunar stroke (Figure 1A+B)
with two-asymtomatic aneurysm of the basilar artery (Figure 1C+D). After
coiling of both (Figure 1E) the patients developed bilateral mydriasis and loss
of consciousness

Figure 3: After one week undulating double vision and right sided mydriasis
(A-D) without ischemic or inflammation correlate with the first MRI scan.

Figure 4: In follow up after one week with worsened symptoms enhanced
mesencephalic oedema and ischemic stroke were seen (Figure 4A-L).

Case 2: A 62-year-old male patient presented with reduced
consciousness, right-sided hemiparesis and dysarthria. About three
weeks before onset, two intracerebral aneurysms were coiled without
complications, one at the top of the basilar artery (Figures 5A and 5C) and another at the left MCA (Figures 5B and 5C). CT scan was negative
for intracranial haemorrhage. CSF was also negative for detection
of haemorrhage, but showed elevated cell count. Empiric antibiotic
treatment with a regime of ceftriaxone and ampicillin, later furthermore
metronidazole and fosfomycin, next to an anti-oedematous treatment
with methylprednisolone was initiated. In further work-up, MRI scan
showed regular position of both coil packages and a local lesion nearby
the coil of the left ACM aneurysm (Figure 5D). A new ischemic lesion
could not be detected. After medical treatment over two weeks, clinical
recovery and reduction of the inflammatory lesion in MRI were seen (Figure 5E). The patient was discharged after restitutio ad integrum.
Occasional amnestic aphasia lasting for few seconds could be correlated
with pathological EEG transformation over the left temporal lobe.
Under medical treatment in a 5-year follow up, the patient presented
stable results in clinical examination, MRI and transcranial ultrasound.

Figure 5: Case 2. 62-year-old patient with two intracerebral aneurysms one
at the top of BA, another at left MCA (Figure 5A-C). Three weeks after coiling
upcomin neurological deficites. MRI showed perianeurysmal inflammatory
lesions responsive to antibiotic and antioedematous treatment.

Results

The first post-interventional set of complications observed in
the first patient still has not been explained satisfactorily. Enhanced
clotting during the endovascular procedures and the primary stroke
made us screen for a coagulation abnormality, which seems likely
but nevertheless remains unproven. There was no thrombotic event
in the patient’s history nor in her family. All known and measurable
coagulopathies including Fabry’s disease were ruled out. The embolic
pattern of the lesions on DWI and the fact that the lesions were located
significantly below the aneurysm neck make it unlikely that the coils
caused the thrombus formation. We therefore propose underlying
endothelial hypersensitivity as a possible cause of the lesions, which
would also reflect the early haemorrhagic transformation of these lesions
as seen in (Figure 2E). Double vision lasting only for seconds to a few
minutes is more likely explained by a malfunction of the third cranial
nerve caused by pulsation of the coiled aneurysm; this is similar to the
neurovascular compression syndromes known to occur with the 5th
cranial nerve. In 1991 Kwan et al. reported an increase in aneurysm size
due to what they called the “water-hammer effect” [1] of pulsatile blood
flow from the basilar artery. In the present case there was no evidence of an increase in aneurysm size, incomplete coil packing, or space
between aneurysm and coils, which makes this hypothesis unlikely.
We discussed the possibility of a neurovascular compression syndrome
and were considering placing the patient on antiepileptic medication
to treat her symptoms when the last set of complications began. Over
time we observed progressive neurological symptoms, which could
be explained by an impairment of the tractus lemniscus medialis. At
that point in our diagnostic investigation, neurovascular compression
as the sole pathological mechanism appeared unlikely. The damage to
the tractus was best explained by local inflammation of the aneurysm
wall leading to mesencephalic oedema. Horie et al. observed similar
oedema, but in their patients the aneurysms had not been completely
obliterated [2]. Overall, the precise mechanism leading to obliteration
of an aneurysm is still unclear, with opposing data obtained in humans
[3,4] and mice [5] concerning the endothelium at the neck of the
aneurysm (Table 1). Considering a normal response of thrombosis,
the release of inflammatory cytokines after platelet activation [6]
in a setting of critical-size of space occupying aneurysm could lead
to an inflammatory response, which in turn leads to even greater
thrombosis: [7,8] a vicious circle of acute thrombosis and worsening
of neurological symptoms. Treatment options in this case seem to be
high doses of steroid medications, as reported by Stracke et al. [9]. In
the first reported case the presumed inflammation proved to be sterile,
with no evidence of bacterial contamination of the coil package [10]
as confirmed by an analysis of the patient’s CSF. In the end we believe
that a small enlargement of the aneurysm following coiling first caused
a neurovascular compression syndrome and, over time, produced
mesencephalic oedema via sterile neurovascular inflammation. In
the second case also an inflammatory lesion after coiling might be
responsible for diverse neurological deficits. The combination of local
inflammatory lesion in MRI with contrast enhancement and elevated
cell count in CSF is also suspect of post-interventional abscess, which
could not be excluded retrospectively. Elevated CSF cell count can
be found in local inflammation as well. Finally, medical treatment
with antibiotical and anti-inflammatory regime was successful.
Possible reasons for neurovascular inflammation after coiling or
implementation of other devices and stents might be contamination of
the material, mechanical irritation or hypersensitivity.

Author

Case/study

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year

Diagnosis

Treatment /problem

Treatment complication

#pat.

Cohen JE

Case

Postembolization perianeurysmal edema as a cause of uncinate seizures.

However, only rare information about this complication exists in
literature. Skolarus et al. describe white matter changes after aneurysm
coiling and hypothesize an exuberant inflammatory response related
to implementation of polyglycolic-polylactic acid coils, however,
bioactive coils were not used in this case [11]. Despite escalating antiinflammatory
and anti-oedematous therapies, the oedema persisted
and eventually a small mesencephalic stroke occurred. Whether this
stroke was caused by obliteration of small perforating arteries or
traction of arteries due to the mass effect of the aneurysm, or whether
it was due to direct compression or indirect compression resulting in
venous congestion is speculative [12,13]. Especially in the first case
obliteration of the aneurysm led to a more pronounced inflammatory
mass effect. This is in contrast to the effect itself mostly described in
the literature: Alleviation of compression by reducing pulsation of the
aneurysm wall [14,15]. We were fortunate that we never were forced
to consider the ultimo ratio treatment option-bilateral occlusion of the
vertebral artery [16]. In addition, coil removal to prevent a progressive
unstoppable mass effect was never part of our discussion [17,18].

We reviewed the literature to see whether a surgical approach may
have been a wiser treatment plan. We found no clear preference for
surgical clipping or endovascular treatment with respect to the critical
size of an aneurysm, localization of the lesion, or already existing neurological symptoms. In 1994 Van Halbach and Higash showed that
endovascular treatment reduces a mass effect [19], whereas in 2004
Heran et al. reported the opposite, favouring surgical clipping in cases
in which a mass effect was present [20]. Regarding critical anatomical
locations, in 2011 Schuss et al. reported a small series of aneurysms
affecting the visual system; these authors found that clipping could
be superior to endovascular treatment in reducing a mass effect.
Concerning treatment complications most available reports are
cases describing clinical symptoms like seizures or symptoms
of hydrozephalus after coiling. Three larger studies found post
interventional wall enhancement and oedema of the coiled aneurysma
in between 6.8 and 18.6% [21-35].

In summary, there are four main complications described in
literature:

• Thrombembolism as a cause of stroke from aneurysmal neck

• Inflammatory response due to coiled and thrombosed
aneurysma

• Mass effect

• Local inflammation by chemical ingredients or contamination
of the coils. These cases emphasize again the necessity of
multimodal treatment choices in patients with complicated
aneurysms of the basilar artery that exert a mass effect, both
with regard to the choice of treatment and the management
of complications like seizures, perianuerysmal edema and
hydrocephalus.

Conclusion

Local symptomatic perianeurysmal oedema with neurovascular
compression syndrome is a rare complication of endovascular
treatment and has to be considered when patients display neurological
symptoms, especially in space-occupying aneurysms. The exact
pathophysiology of this complication remains nebulous; however,
contamination of the coil, thrombosis, local cytokine release by
mechanical irritation and a specific reaction to the coil material may be
responsible. Administration of corticosteroids, platelet inhibitors, and
hyperosmolar therapy may be therapeutic and, overall, the long-term
prognosis for these patients is good.

Acknowledgment

Author thanks Jo Ann M. Eliason, MA, ELS, for her assistance in the editing
of this paper.

Conflict of Interest

The authors report no conflicts of interest related to this study or preparation
of the paper.